Lysine 63-linked polyubiquitin potentially partners with p62 to promote the clearance of protein inclusions by autophagy

摘要: Although protein inclusions associated with neurodegenerative diseases are typically enriched ubiquitin, it is currently unclear whether the topology of ubiquitin linkage plays a role in their biogenesis. In an attempt to clarify this, our recent work identified K63-linked polyubiquitin as key regulator inclusion dynamics. We found setting ectopic overexpression different species cultured cells that ubiquitination promotes formation and autophagic clearance linked several major diseases. Further supporting we report here similar phenomenon co-expressing Ubc13 Uev1a but not those expressing UbcH7 or UbcH8. Notably, association known promote ubiquitination. exploring how could by autophagy, also current study interacts p62, ubiquitin-binding previously demonstrated others facilitate autophagymediated inclusions. Further, K63 ubiquitin-positive were be p62. Given observed intimate relationship between p62 polyubiquitin, results suggest may function partners involved directing autophagy.